Alzheimer Disease, Familial Early-Onset, With Coexisting Amyloid And Prion Pathology


Clinical Features

Leuba et al. (2000) described a Swiss family whose members presented with standard clinical and neuropathologic features of Alzheimer disease (104300) and, in particular, severe neurofibrillary tangle degeneration present in the hippocampus and in several cortical areas, together with a large number of beta-amyloid deposits and senile plaques. The brain pathology of 5 deceased members of this family, from 2 generations, represented a coexisting beta-amyloid and prion protein (PrP; 176640) pathology. Frequent beta-amyloid-positive senile plaques were observed, together with senile plaques stained by the monoclonal antibody against PrP(106-126). In all 5 cases, the cerebral cortex showed spongiform changes, mainly in the superficial layers, with some degree of gliosis. Successive sections showed that both beta-amyloid- and PrP-positive senile plaques were deposited in all layers of the frontal and temporal cortex. More than 50% of senile plaques were immunopositive for both beta-amyloid and PrP(106-126) antibodies. The proportion of senile plaques marked for each antibody alone was smaller, and, in particular, senile plaques marked for PrP(106-126) represented only 5 to 10% of the whole population.

Molecular Genetics

In 5 deceased members from a Swiss family with early-onset Alzheimer disease with coexisting beta-amyloid and prion protein pathology, Leuba et al. (2000) did not identify mutations in the beta-amyloid precursor protein (104760), presenilin-1 (104311), or presenilin-2 (600759) genes.